EPILEPSY AND SEIZURES A DEEP INSIGHT PRESENTED BY

EPILEPSY AND SEIZURES- A DEEP INSIGHT PRESENTED BY: VISHNU. R. NAIR, 4 TH YEAR PHARM. D, NATIONAL COLLEGE OF PHARMACY, KERALA UNIVERSITY OF HEALTH SCIENCES(KUHS),

INDEX/ CONTENTS OF THIS PPT : 1. 2. 3. 4. 5. 6. 7. 8. 9. GENERAL ACKNOWLEDGEMENT GENERALIZED TERMINOLOGIES EPIDEMIOLOGY TYPES OF EPILEPSIES{INCLUDING CLINICAL MANIFESTATIONS} ETIOLOGY OF EPILEPSY PATHOPHYSIOLOGY OF EPILEPSY RISK FACTORS FOR SEIZURES DIAGNOSIS OF EPILEPSY MANAGEMENT STRATEGIES FOR EPILEPSY

GENERAL ACKNOWLEDGEMENT : TO THE ALMIGHTY , MY NEAR AND DEAR ONES… AND TO ALL READERS WORLDWIDE!!! THANKFUL TO ALL FOR UR SUPPORT, GUIDANCE AND ENCOURAGEMENT……………… ITS BEEN A REALLY HARD JOB WORKING ON THIS PPT………………… HOPE U LIKE IT!! HAPPY READING!!!

GENERALIZED TERMINOLOGIES : 1. SEIZURE: “PHENOMENON, characterized by an EXCESSIVE, HYPERSYNCHRONOUS DISCHARGE of CORTICAL NEURONAL ACTIVITY, (measured by EEG), featured by DISTURBANCES in CONSCIOUSNESS, SENSORY MOTOR SYSTEMS, SUBJECTIVE WELL-BEING and OBJECTIVE BEHAVIOUR…………………” 2. EPILEPSY: “CHRONIC SEIZURE DISORDER/ GROUP OF DISORDERS, characterized by SEIZURES, that usually occur UNPREDICTABLY, in the ABSENCE of a SUBSTANTIAL PROVOKING FACTOR……………. ” 3. CONVULSION: “VIOLENT, INVOLUNTARY CONTRACTIONS of VOLUNTARY MUSCLES, which may/ may not be present in epilepsy/ seizure disorder………. . . ”

EPIDEMIOLOGY OF EPILEPSY : - Higher risk observed in extremes of age - Prevalence in European countries is 0. 5% - Prevalence in developing countries is higher, due to parasitic illnesses like CYSTICERCOSIS - Around 50 million people worldwide have epilepsy - Epilepsy responds to treatment in 70% cases - 75% people in developing countries do not get required anti-epileptic treatment…………………. .

TYPES OF EPILEPSIES (INCLUDING CLINICAL MANIFESTATIONS) : Based on INTERNATIONAL LEAGUE AGAINST EPILEPSY(ILAE) classification: 1. PARTIAL SEIZURES (FOCAL SEIZURES) 2. GENERALIZED SEIZURES ……………………

1. PARTIAL SEIZURES (FOCAL SEIZURES): - Most common seizure type - Localized to a neuronal system, limited to PART OF 1 CEREBRAL HEMISPHERE - Types include: A. SIMPLE PARTIAL SEIZURES: - Not associated with loss of consciousness - Associated with: MOTOR SIGNS (Convulsive jerking, lip smacking) ii. SENSORY & SOMATOSENSORY SIGNS (Paresthesias, auras) iii. AUTONOMIC SIGNS (Sweating, flushing) iv. BEHAVIOURAL MANIFESTATIONS (Dysphasia, structured hallucinations) i.

B. COMPLEX PARTIAL SEIZURES: - Associated with IMPAIRED CONSCIOUSNESS - Impairment precedes/ follows seizures - Associated with: i. Purposeless behavior ii. Glassy stare iii. Aimless walking iv. Hallucinations (visual, auditory) v. Aggressive behaviour……………….

2. GENERALIZED SEIZURES: - Diffuse seizures - Affect BOTH CEREBRAL HEMISPHERES - Types include: A. IDIOPATHIC EPILEPSIES: - Age related onset - Also congenital (genetic origin) B. SYMPTOMATIC EPILEPSIES: - Aftermath of a DOCUMENTED UNDERLYING CNS DISORDER C. CRYPTOGENIC EPILEPSY: - Cause unknown - Presumed to be age- related

Manifestations of generalized seizures include: A. ABSENCE SEIZURES: a. b. Also known as ‘PETIT MAL’ seizures Alterations of consciousness, lasting 10 -30 mins. Occurs Associated with: Staring, with occasional eye-blinking Enuresis B. MYOCLONIC SEIZURES: - Also known as ‘BILATERAL MASSIVE EPILEPTIC MYOCLONUS’ - Associated with INCVOLUNTARY, RHYTHMIC JERKING of FACIAL, LIMB/ TRUNK MUSCLES C. CLONIC SEIZURES: - Associated with SUSTAINED MUSCLE CONTRACTIONS, alternating with RELAXATION

D. TONIC SEIZURES: - Associated with SUSTAINED MUSCLE CONTRACTIONS (Stiffening) E. GENERALIZED TONIC-CLONIC SEIZURES (GTCS): - Also known as ‘GRAND MAL’ seizures - Causes sudden loss of consciousness - Individual becomes rigid and falls to the ground - Interrupted respirations - Extended legs - Lasts for 1 min. - Rapid bilateral muscle jerking - Heavy salivation, tongue biting, headache, confusion - In some cases, GRAND MAL seizures occurs repeatedly, with no recovery of consciousness between attacks, leading to state known as ‘STATUS EPILEPTICUS’………………. .

F. ATONIC SEIZURES: - Also known as ‘DROP ATTACKS’ - Sudden loss of postural tone individual falls to the ground - Occurs mainly in children…………………. .

ETIOLOGY OF EPILEPSY : Mainly we will see the causes of: A. FOCAL SEIZURES B. GENERALIZED SEIZURES……………. .

1. CAUSES OF FOCAL SEIZURES: Include: A. IDIOPATHIC REASONS: - Benign ROLANDIC epilepsy of childhood (Discovered by Italian Anatomist Luigi Rolando) - Benign OCCIPITAL epilepsy of childhood B. GENETIC REASONS: - Tuberous sclerosis (characterized by tiny benign tumours {angiofibromas} on the face, skin, and abnormalities of kidney, brain and heart) - Autosomal dominant frontal lobe epilepsy - Autosomal dominant partial epilepsy with auditory features (ADPEAF) - Von Hippel-Lindau disease (characterized by hemangioblastomas {benign blood vessel tumours } in brain, spinal cord, retina; kidney cysts & cancer and pheochoromocytomas} - Neurofibromatosis (causes tumours to grow on nerves and inhibits neural growth) - Cerebral migration abnormalities

C. INFANTILE HEMIPLEGIA (acute hemiparesis, that occurs in infancy, caused by vascular accidents, like cerebral infarction or thrombosis) D. DYSEMBRYONIC CAUSES: - Cortical dysgenesis - Sturge-Weber syndrome (mainly affects the skin, featured by ‘port wine stain birthmark’; also known as ‘Encephalotrigeminal angiomatosis’) E. MESIAL TEMPORAL SEIZURES: - Associated with febrile convulsions F. CEREBROVASCULAR DISEASES: - Intracerebral hemorrhage Cerebral infarction Arteriovenous malformation Cavernous hemangioma (occurs on body surface, as red or purplish, blood filled lakes/ channels)

G. PRIMARY AND SECONDARY TUMOURS H. TRAUMA (including neurosurgery) I. INFECTIVE CAUSES: - Cerebral abscess (pyogenic) - Subdural empyema - Toxoplasmosis - Encephalitis - Cysticercosis - HIV infections J. INFLAMMATORY CAUSES: - Sarcoidosis - Vasculitis……………. . - Tuberculoma

2. CAUSES OF GENERALIZED SEIZURES : Includes: A. GENETICS: - Inborn metabolism errors sclerosis) - Storage diseases B. CEREBRAL BIRTH INJURY C. HYDROCEPHALUS D. CEREBRAL ANOXIA E. ALCOHOL WITHDRAWAL F. TOXINS: - Organophosphates (SARIN) - Heavy metals (LEAD, TIN) - Phacomatoses (Tuberous

G. DRUGS: - ANTIBIOTICS (Penicillin, metronidazole, Isoniazid) ANTIMALARIALS (Chloroquine, mefloquine) CYCLOSPORINE ANTI-ARRRHYTHMICS (Lidocaine, disopyramide) PSYCHOTROPICS (Phenothiazines, TCAs, Lithium) AMPHETAMINE WITHDRAWAL H. METABOLIC DISEASE : - Hypocalcemia Hyponatremia Hypomagnesemia Hypoglycemia Renal failure Liver failure

I. INFECTIVE CAUSES: - Post- infective encephalopathy - Meningitis J. INFLAMMATORY CAUSES: - Multiple sclerosis - SLE K. DIFFUSE DEGENERATIVE DISEASES: - Alzheimer’s disease - CREUTZFELDT- JAKOB DISEASE (Degenerative, invariably fatal brain disorder, associated with failing memory , behaviour changes, weakness of extremities, mental deterioration and coma)………………. .

PATHOPHYSIOLOGY OF EPILEPSY : 1. Neurons are inter-connected in a complex network 2. Each individual neuron linked via synapses with hundreds of others 3. Neurons discharge electrical current neurotransmitters are released at synaptic levels permits inter- communication 4. Neurotransmitters are of 2 types: a. INHIBITORY NEUROTRANSMITTER (GABA): - GABA (Gamma amino butyric acid ) acts on ion channels increases chloride inflow decreases chances of action potential formation b. EXCITATORY NEUROTRANSMITTER ( ASPARTATE, GLUTAMATE): - Above agents allow sodium and calcium influx paves way for action potential formation 5. In this manner, information is conveyed, transmitted and processed throughout the CNS 6. Imbalance between above excitation and inhibition seizures occur

7. A normal neuron discharges repetitively at LOW BASELINE FREQUENCIES 8. If neurons are damaged, injured/ suffer a chemical/ metabolic insult changes in discharge pattern develops 9. During epilepsy regular low frequency discharges are replaced by BURSTS of HIGH FREQUENCY DISCHARGES followed by periods of INACTIVITY 10. A single neuron discharging in an abnormal manner is usually not clinically significant 11. When a WHOLE POPULATION of NEURONS DISCHARGE SYNCHRONOUSLY in an ABNORMAL MANNER EPILEPTIC SEIZURE IS PRECIPITATED 12. This abnormal discharge may remain LOCALIZED/ it may SPREAD TO ADJACENT AREAS, RECRUITING MORE NEURONS as it EXPANDS……………….

RISK FACTORS FOR EPILEPSIES : 1. Sleep deprivation 2. Missed doses of anti-epileptic drugs(AEDs) in treated patients 3. Alcohol withdrawals 4. Recreational drug misuse 5. Physical and mental exhaustion 6. Flickering lights (includes TV, computer screens; comes under generalized epilepsy syndrome) 7. Intercurrent infections 8. Metabolic disturbances 9. UNCOMMON REASONS: - Loud noises - Very hot baths…………………

DIAGNOSIS OF EPILEPSIES : Based on the following criteriae: 1. TO CHECK THE LOCATION OF EPILEPTIC ORIGIN: - Standard EEG - Sleep EEG - EEG, with special electrodes 2. TO CHECK FOR STRUCTURAL LESIONS: - CT SCAN - MRI SCAN 3. FOR METABOLIC DISORDER DIAGNOSIS: - Urea and electrolytes - Blood glucose levels - LFTs - Serum calcium and magnesium levels

4. FOR INFLAMMATORY/ INFECTIVE DISORDER DIAGNOSIS: - CBC - ESR - CRP TEST - CHEST XRAY - SEROLOGY FOR SYPHILIS, HIV, COLLAGEN DISEASE - CSF EXAMINATION 5. FOR CONFIRMING ATTACKS TO BE OF EPILEPTIC ORIGIN: - Ambulatory EEG - Video telemetry 6. BRAIN IMAGING: Indicated for: - Epilepsy starting after 16 yrs. of age - Seizures, with clinical focal features - EEG, showing a focal seizure source

MANAGEMENT OF EPILEPSY : Includes: 1. GOALS OF THERAPY 2. GENERAL GUIDELINES FOR ANTICONVULSANT THERAPY 3. PHARMACOTHERAPY 4. GUIDELINES FOR CHOICE OF ANTI-EPILEPTIC DRUGS(AEDs) 5. NON-PHARMACOTHERAPY/ PATIENT- COUNSELLING TIPS+ HOME REMEDIES FOR EPILEPSY

1. GOALS OF THERAPY : 1. To control and reduce SEIZURE FREQUENCY 2. To focus on MINIMUM POSSIBLE DOSAGE OF AEDs 3. To minimize ADRs associated with therapy 4. To ensure PATIENT MEDICATION COMPLIANCE 5. To ensure that person lives a normal life as far as possible 6. To balance COMPLETE SUPPRESSION of SEIZURES against ADR TOLERABILITY 7. To reduce MORBIDITY and MORTALITY 8. To improve QUALITY OF LIFE(QOL)………………. .

2. GENERAL GUIDELINES FOR ANTICONVULSANT THERAPY : 1. Start with 1 FIRST LINE DRUG 2. Start with a low dose gradually increase dose until effective control of seizures is achieved/ ADRs develop 3. Optimize compliance (use minimum no. of doses/ day) 4. If 1 st line drug fails (seizures continue/ ADRs develop) start 2 nd (1 st line drug) , followed (if possible) , by gradual withdrawal of the drug presently being used 5. If 2 nd line drug fails (due to above reasons) start 2 nd line drug, in combination with preferred 1 st line drug at maximum tolerated doses (keep in mind possible interactions) 6. If above combination fails (due to above reasons) replace 2 nd line drug with alternative 2 nd line drug

7. If above combination fails (due to above reasons) check compliance & reconsider diagnosis, based on the following criteriae: a. If the events are seizures/ not b. Presence absence of occult lesions c. Treatment compliance/ alcohol/ drugs confounding responses 8. Consider alternative, non-drug treatments, like: a. Epilepsy surgery b. Vagal nerve stimulation 9. Use minimum number of drugs in combination at any one time…………….

3. PHARMACOTHERAPY : A. BARBITURATES : Include: I. PHENOBARBITONE (LUMINAL): - Drug has 3 actions: a. Drug depresses sensory, motor cortex and cerebellum b. Drug acts on GABA(A) receptors increases synaptic inhibition increases seizure threshold and decreases spread of seizure activity from a seizure focus c. Drug inhibits CALCIUM channels decreases excitatory transmitter release - ADR : a. Sedation b. Respiratory depression (when given i. v) c. Headache

a. a. b. DRUG INTERACTION: Phenobarbital + oral contraceptives decreased efficacy of latter USES: Febrile convulsions (8 mg/kg/day; child) GTC c. Neonatal seizures d. Status Epilepticus (SE) B. DEOXYBARBITURATES : Includes: I. PRIMIDONE (MYSOLINE): - MOA: Drug enters body metabolized by liver to PHENOBARBITONE Shows remaining effects - ADR: a. STEVEN-JOHNSON SYNDROME (SJS) b. Hypotension c. Hepatitis

- DRUG INTERACTION: a. BZDs + Drug increased sedation - USES: A. GTCS (250 -500 mg BD) B. Partial epilepsy C. HYDANTOINS : Includes: A. PHENYTOIN (BARBITOIN): - Drug has 3 actions: i. Drug promotes sodium efflux/ decreased sodium influx from membranes in motor cortex neurons ii. Drug stabilizes neuronal membranes iii. Drug slows conduction velocity

- ADR: Gingival hyperplasia ii. Hirsutism iii. Megaloblastic anemia iv. Diabetes mellitus v. FETAL HYDANTOIN SYNDROME (Drug used in pregnancy causes hare lips, microcephaly in neonates etc) - DRUG INTERACTIONS: a. Drug + Pyridoxine(in high dose) decreased levels of phenytoin - USES: a. Tonic clonic seizures b. SE (10 -15 mg/kg i. v/ infusion) i.

B. FOSPHENYTOIN (FOSPHEN): - MOA: Drug converted to PHENYTOIN after injection shows actions of PHENYTOIN - ADR: a. Hypersensitivity b. SJS c. Hepatotoxicity - DRUG INTERACTIONS: a. Drug + CBZ(Carbamazepine) decreased CBZ efficacy - USES: a. Seizures, associated with NEUROSURGERY/ HEAD INJURY b. SE (20 mg/kg i. v)………….

D. IMINOSTILBENES : Includes: A. CARBAMAZEPINE (CARBATOL): - Drug shows 2 actions: i. Drug stabilizes inactivated state of sodium channels makes neurons less excitable ii. Drug decreases activity of NUCLEUS VENTRALIS of thalamus / synaptic transmission associated with neuronal discharge - ADR: a. SJS b. Arrhythmia c. CHF - DRUG INTERACTIONS: a. Drug + warfarin decreased anticoagulant effect - USES : a. Trigeminal neuralgia c. Epilepsy (200 -400 mg TDS) b. Bipolar disorder

B. OXCARBAZEPINE (CARBOX): - Drug shows 5 actions: Drug blocks sodium channels stabilizes neuronal membranes ii. Drug inhibits repetitive firing iii. Drug reduces synaptic impulse propagation iv. Drug increases potassium conductance v. Drug modulates activity of high voltage activated calcium channels - ADR: a. SJS b. Hepatitis c. Pancreatitis - DRUG INTERACTION: a. Furosemide + drug increased risk of HYPONATREMIA - USES : a. Partial seizures , with/ without secondary generalization (in adults: 0. 6 -2. 4 g/day, in divided doses)………… i.

E. SUCCINIMIDES: Includes: A. ETHOSUXIMIDE (ZARONTIN): - Drug shows 2 actions: Drug depresses nerve transmission in motor cortex ii. Drug increases convulsive stimuli threshold in CNS - ADR: a. GI disturbances b. Dizziness - DRUG INTERACTION: a. Drug + sodium oxybate pharmacodynamic synergism increased toxicity of each other additive CNS depression - USE: a. Absence seizures : 500 mg P/O QID…………. i.

F. ALIPHATIC CARBOXYLIC ACIDS: Includes: I. VALPROIC ACID (VALPROL): - Drug shows 3 actions: i. Drug increases GABA levels in brain ii. Drug increases / mimics action of GABA at postsynaptic receptor sites iii. Drug inhibits sodium and calcium channels - ADR: a. SJS b. Pancreatitis c. Thrombocytopenia - DRUG INTERACTION: a. Drug + Chlorpromazine severe HEPATOTOXICITY - USES: a. Complex partial seizures (For adults: max. 60 mg/kg/day) b. Simple and complex absence seizures…………………. .

II. DIVALPROEX (DIVAA): - MOA : Same as that of SODIUM VALPROATE - ADR: a. Increased bleeding time b. Encephalopathy c. Dementia - DRUG INTERACTION : a. Drug + cholestyramine decreased levels of divalproex - USES : a. Complex partial seizures (max. : 60 mg/kg/day) b. Mania c. Migraine prophylaxis d. Simple and complex absence seizures………………

G. BENZODIAZEPINES : Includes: I. CLONAZEPAM (CLONA): - Long acting BZD - Drug shows 3 actions: a. Drug increases presynaptic GABA inhibition b. Drug decreases monosynaptic and polysynaptic reflexes c. Drug facilitates GABA neurotransmission and other inhibitory neurotransmitters suppresses muscle contractions - ADR: a. Blood disorders b. Increased LFTs - DRUG INTERACTION: a. Amiodarone + drug increased drug toxicity c. Respiratory depression

- USES: a. Panic disorder b. Seizure disorders (For adult: up to 1. 5 g , in 3 divided doses) c. SE II. CLOBAZAM (CLOBA): - 1, 5 - BENZODIAZEPINE (Contrary to others) - MOA: Drug binds to GABA(A) receptor potentiates GABA- ergic neurotransmission - ADR: a. Hypotension b. Respiratory depression c. Jaundice - DRUG INTERACTION: a. CBZ + Clobazam decreased drug levels b. Alcohol + Clobazam increased drug levels

III. DIAZEPAM (DIZEP): - Drug shows 2 actions: a. Drug modulates postsynaptic effects of GABA(A) transmission results in an increase in presynaptic inhibition b. Drug acts on part of limbic system, thalamus and hypothalamus induces CALMING EFFECT - ADR: a. Respiratory depression b. Hypotension c. Jaundice - DRUG INTERACTION: a. Hormonal contraceptives + Drug increased drug effects increased incidence of BREATH-THROUGH BLEEDING

- USES: a. STATUS EPILEPTICUS (Adult: 5 -10 mg every 5 -10 mins. ; maximum 30 mg. ) b. Anxiety c. Conscious sedation for procedures d. Ethanol withdrawal e. Insomnia associated with anxiety f. Muscle spasm with tetanus g. Night terrors h. Sedation Skeletal muscle relaxation j. Sleep walking………………. . i.

IV. LORAZEPAM (LOPEZ): - Short onset of effect - Long half-life - Drug shows 2 actions: a. Drug increases action of GABA b. Drug depresses all levels of CNS, including lumbar and reticular formation - ADR: a. Respiratory depression b. Hypotension - DRUG INTERACTIONS: a. Loxapine + drug increased respiratory depression b. Zidovudine + drug increased headache c. Jaundice

- USES: a. Antiemetic (adjuvant therapy) b. Acute anxiety c. Insomnia associated with anxiety d. Panic disorder e. Pre-operative medication f. Sedation g. SE (For adult: 4 mg; repeat once after 10 mins, if necessary)……………. .

H. PHENYLTRIAZINES: Includes: LAMOTRIGINE (LAMORIN): a. b. a. a. a. b. Drug shows 2 actions: Drug inhibits release of excitatory amino acids (glutamate) Drug inhibits voltage sensitive sodium channels stabilizes neuronal membranes ADR: SJS b. DIC c. Lymphadenopathy DRUG INTERACTION: Drug + Phenytoin/Phenobarbital decreases levels of drug USES: Bipolar disorder GTC( For adult: 25 mg/day for initial 14 days then increase dose to 50 mg/day for next 14 days then increase dose to 50 -100 mg/day for next 7 -14 days)…………. .

I. CYCLIC GABA ANALOGUES: Includes: A. GABAPENTIN (GABAPENTIN): - Structurally related to GABA, but has no effect on GABA binding, uptake/ degradation - MOA: Drug modulates voltage sensitive calcium channels decreases entry of calcium into presynaptic neurons decreases glutamate release decreases neuronal excitability - ADR : a. SJS b. ARF c. Hepatitis - DRUG INTERACTION: a. Drug + phenytoin/antacids decreased levels of latter

- USES: a. Diabetic neuropathy b. Focal seizures, with/ without secondary generalization (For child: 12 -18 yrs 300 mg TID/ 0. 9 -3. 6 g/day , in 3 divided doses) c. Restless legs syndrome d. Post- therpetic neuralgia / neuropathic pain……………… B. PREGABALIN (PREGALIN): - Drug shows 2 actions: Drug binds to a subunit of voltage gated calcium channels in CNS remaining same as GABAPENTIN ii. Does not affect sodium channels - ADR: a. Primary AV block b. CHF c. SJS i.

- DRUG INTERACTIONS: a. Drug + Lorazepam/ alcohol increased efficacy of latter - USES: a. Partial seizures, with/ without secondary generalization (50 -300 mg/day, in 2 -3 divided doses, for adults; maximum: 600 mg/day) b. Anxiety c. Peripheral and central neuropathic pain d. Fibromyalgia………………. .

J. NEWER DRUGS: Include: I. TOPIRAMATE II. ZONISAMIDE III. LEVETIRACETAM IV. VIGABATRIN V. TIAGABINE VI. LACOSAMIDE VII. FELBAMATE VIII. RUFINAMIDE IX. STIRIPENTOL X. ESLICARBAZEPINE ACETATE XI. PERAMPANEL…………………. .

I. TOPIRAMATE (TOPIRATE): - CLASS: SULFAMATE SUBSTITUTED DERIVATIVE - Drug shows 2 actions: a. Drug inhibits neuronal voltage dependent sodium channels b. Drug enhances activity of GABA - ADR: a. SJS necrolysis(TEN) b. Thrombocytopenia - DRUG INTERACTION: a. Zonisamide+ drug increased risk of renal calculi - USES: a. Epilepsy (200 -1000 mg/day) b. Migraine prophylaxis c. Partial seizures………………. c. Toxic epidermal

II. ZONISAMIDE (ZONICARE): - CLASS: SULFONAMIDE DERIVATIVE (Benzisoxazole compound) - Drug shows 3 actions: a. Drug acts at sodium and calcium channels stabilizes neuronal membranes b. Does not affect GABA activity c. More active against TONIC PHASE than against CLONIC PHASE - ADR: a. SJS b. TEN c. Rhabdomyolysis - DRUG INTERACTION: a. CBZ+ Zonisamide decreased level of Zonisamide (by affecting CYP 3 A 4 metabolism) - USES: a. Partial seizures, with/ without secondary generalization (300 -500 mg/ day; in 1 -2 divided doses)…………………. .

III. LEVETIRACETAM (LEVACETAM): - CLASS: PYRROLIDINE DERIVATIVE - Drug shows 3 actions: a. Drug inhibits voltage dependent N-TYPE CALCIUM CHANNELS b. Drug binds to synaptic proteins modulate neurotransmitter release c. Drug displaces negative modulators facilitates GABA- ergic inhibitory transmission - DRUG INTERACTION: a. CBZ + Drug CBZ toxicity occurs - ADR: a. Thrombocytopenia b. Pancreatitis c. Hepatic dysfunction - USES: a. GTC (Max: 1. 5 g BID; For adults) b. Myoclonic seizures c. Partial seizures, with or without secondary generalization………………….

IV. VIGABATRIN (SABRIL): - CLASS: GAMMA-VINYL GABA DERIVATIVE - MOA: Drug irreversibly inhibits GABA-transaminase increases GABA levels in brain - ADR: a. Weight gain in children (47%) b. Permanent bilateral concentric visual field constriction (>30%) c. Fatigue (28%) - DRUG INTERACTION: a. Drug + CLOBAZAM Increased sedation, respiratory depression - USES: a. Complex seizures (1. 5 g BID) b. Partial seizures c. Infantile spasms d. Refractory complex seizures…………….

V. TIAGABINE (GABITRIL): - CLASS: GABA REUPTAKE INHIBITOR - MOA: drug blocks GABA reuptake by presynaptic neuron increases its activity in nervous system - ADR: a. Dizziness (26 -30%) b. Asthenia (16 -20%) c. Somnolence (16 -20%) - DRUG INTERACTION: a. Drug + Clobazam increased sedation/ respiratory depression - USES: a. Partial seizures (with hepatic enzyme inducing anticonvulsants) b. Partial seizures (without hepatic enzyme inducing anticonvulsants; 12 -22 mg/day , divided in 2 -3 doses)…………………

VI. LACOSAMIDE (LACOSAM): a. b. c. a. a. CLASS : HOMOSERINAMIDE DERIVATIVE; FUNTIONAL AMINO ACID Drug shows 2 actions: Drug slowly inactivates voltage gated sodium channels Drug binds to collapsin response mediator protein-2 (CRMP-2); a phosphoprotein; expressed mainly in nervous system modulates neuronal differentiation and axonal outgrowth ADR: Dizziness (31%) d. Atrial fibrillation Diplopia (11%) e. Atrial flutter Headache (11%) f. Suicidal ideation DRUG INTERACTION: Drug + anti- arrhythmics enhanced PR-prolongation USES: Neuropathic pain b. Partial seizures (200 -400 mg/day)…….

VII. FELBAMATE (FELBATOL): - CLASS : CARBAMATE DERIVATIVE - Drug shows 2 actions: a. Drug positive modulator of GABA(A) receptor b. Drug blocks NMDA receptors (NR 2 B subunit) - ADR: a. Anorexia b. Liver failure c. Aplastic anemia - DRUG INTERACTION: a. Felbamate + clopidogrel decreased effects of clopidogrel - USES: a. Partial seizures, with/ without secondary generalization (Adults: 1, 200 mg Q 6 H/Q 8 H) b. Partial/ Generalized seizures , associated with LENNOX-GASTAUT SYNDROME …….

VIII. RUFINAMIDE (BANZEL): - CLASS : TRIAZOLE DERIVATIVE - MOA: Drug modulates activity of sodium channels prolongs their inactive state limits repetitive firing of sodium dependent action potentials anticonvulsant effect - ADR: a. Diplopia b. SJS c. Dizziness - DRUG INTERACTION : a. Rufinamide + alprazolam decreased levels/ effects of latter - USE: a. LENNOX-GASTAUT SYNDROME (3, 200 mg/day maximum, in 2 divided doses)………………. .

IX. STIRIPENTOL (DIACOMIT): a. b. c. d. e. a. b. c. CLASS: AROMATIC ALLYLIC ALCOHOLS Drug shows 5 actions: Drug increases GABA transmission Drug increases duration of opening of GABA(A) receptor channels in hippocampal areas enhances central GABA transmission Drug increases GABA levels in brain tissues by interfering with its uptake & metabolism Drug inhibits LACTATE DEHYDROGENASE Makes neurons less prone to fire action potentials Drug improves effectiveness of other anti-convulsants…………… ADR: Hyperkinesia Drowsiness Ataxia

a. a. b. c. DRUG INTERACTION: Drug + CBZ/ Phenobarbital increased efficacy/ potency of latter USES: DRAVET SYNDROME (Along with sodium valproate and Clobazam; 50 mg/kg/day) Epilepsy in infancy Refractory childhood epilepsy( in combination with CBZ)…………. X. ESLICARBAZEPINE ACETATE (ESLIZEN): - CLASS : DIBENZAPINE CARBOXAMIDE DERIVATIVE - Drug shows 3 actions: a. PRODRUG activated to ESLICARBAZEPINE/ S-LICARBAZEPINE (Major active metabolite of OXCARBAZEPINE) Blocks sodium channels inhibits repetitive firing decreases synaptic impulse propagation stabilizes neuronal membranes b. Drug increases potassium conductance c. Drug modulates activity of high voltage gated activated calcium channels

- ADR: a. Blurred vision b. HTN c. Peripheral edema - DRUG INTERACTION: a. Drug + Phenytoin/ Barbiturates decreased drug levels - USE: a. Partial onset seizures (for adult: 400 mg/day; for 7 days)……………….

XI. PERAMPANEL (FYCOMPA): - CLASS : NON-COMPETITIVE AMPA RECEPTOR ANTAGONIST) - MOA: Drug non- competitively blocks ALPHA-AMINO-3 -HYDROXY-5 -METHYL-4 ISOXAZOLEPROPIONIC ACID (AMPA ) glutamate receptor on post synaptic neurons decreased glutamate activity decreases neurological disorders causes by glutamate overexcitation - ADR: a. Dizziness (16 -43%) b. Somnolence (9 -18%) c. Suicidal ideation (notorious) - DRUG INTERACTION: a. Drug +CBZ Decreased perampanel effectiveness - USES: a. Partial onset seizures (8 -12 mg/day) b. Tonic clonic seizures……………….

4. GUIDELINES FOR CHOICE OF ANTIEPILEPTIC DRUGS : A. FOR FOCAL ONSET AND / SECONDARY GTCS: - IST LINE DRUG : LAMOTRIGINE - 2 ND LINE DRUGS : CBZ, LEVETIRACETAM, VALPROIC ACID, TOPIRAMATE , ZONISAMIDE, LACOSAMIDE - 3 RD LINE DRUGS: CLOBAZAM, GABAPENTIN, OXCARBAZEPINE, BARBITURATES , PHENYTOIN, PREGABALIN, PRIMIDONE, TIAGABINE…. . B. FOR GTCS: - 1 ST LINE DRUGS : VALPROIC ACID, LEVETIRACETAM - 2 ND LINE DRUGS : LAMOTRIGINE, TOPIRAMATE, ZONISAMIDE - 3 RD LINE DRUGS : CBZ, PHENYTOIN, PRIMIDONE, BARBITURATES……………

C. FOR ABSENCE SEIZURES : - 1 ST LINE DRUG : ETHOSUXIMIDE - 2 ND LINE DRUGS : SODIUM VALPROATE - 3 RD LINE DRUGS : LAMOTRIGINE, CLONAZEPAM…………… D. FOR MYOCLONIC SEIZURES: - 1 ST LINE DRUG: SODIUM VALPROATE - 2 ND LINE DRUGS : LEVETIRACETAM, CLONAZEPAM - 3 RD LINE DRUGS : LAMOTRIGINE, PHENOBARBITAL……………

5. NONPHARMACOTHERAPY/PATIENTCOUNSELLING TIPS +HOME REMEDIES 1. AVOID ACTIVITIES, WHERE PATIENTS MAY PLACE FOR EPILEPSY : THEMSELVES/ OTHERS AT RISK, IF THEY HAVE A SEIZURE (APPLIES AT WORK, HOME/ AT LEISURE) 2. TAKE ONLY SHALLOW BATHS/ SHOWERS 3. AVOID PROLONGED CYCLE JOURNEYS , UNLESS REASONABLE FREEDOM FROM SEIZURES HAS BEEN ACHIEVED 4. ACTIVITIES, THAT REQUIRE PROLONGED PROXIMITY TO WATER (FISHING SWIMMINING, BOATING ) SHOULD BE

5. RECONGIZED MORTALITY OF EPILEPSY SHOULD BE DISCUSSED AT THE TIME OF DIAGNOSIS, AIMED AT MOTIVATING THE PATIENT, TO ADAPT TO HABITS AND LIFESTYLE, TO OPTIMIZE EPILEPSY CONTROL 6. COCONUT OIL: - Highly effective Fatty acids (medium chain triglycerides) in oil possess therapeutic effects on brain cells Oil supplies energy for brain cells relieves epilepsy symptoms Use 1 -3 tsp of EXTRA VIRGIN COCONUT OIL (3 times a day) 7. EPSOM SALT: - EPSOM SALT Contains magnesium sulphate changes psychochemical cell relationships in the brain reduces frequency of seizures and convulsions - Use in the form of: a. Epsom salt bath (2 -3 times/ week) b. Add half tsp of salt to orange juice / water drink every morning

8. LIME: a. b. Popular Ayurvedic remedy Lime helps improve blood circulation to brain Also normalizes excess calcium that may hamper brain functionality Use in the form of: (2 tsp. lime juice + half tsp. baking soda + water) drink daily before going to bed Apply lime juice on head massage thoroughly for a few mins. do daily before taking a shower 9. GARLIC: - Garlic possesses ANTIOXIDANT, ANTISPASMODIC & ANTI-INFLAMMATORY PROPERTIES Promotes proper functioning of nervous, along with destruction of harmful free radicals in body prevents seizures and related symptoms - Use it in the form of: a. Mix half cup of milk + half cup water boil add 4 -5 crushed garlic cloves strain and drink it once daily b. Garlic supplements (under doctor advice)

10. PASSIONFLOWER : - Herb contains CHRYSIN increases GABA amount in brain decreases seizures frequency, anxiety - Use it in the form of : a. CAPSULE, TABLET FORMS b. HERBAL TEA (1 -2 CUPS) - Avoid in pregnancy/ lactation 11. WINTER MELON: a. b. Also known as ‘ASH GOURD’ Popular Ayurvedic remedy Vegetable helps keeps nervous system healthy Also ensures smooth functioning of brain cells Use in the form of: Half glass winter melon juice + little sugar drink in the morning on empty stomach Extract juice of crushed winter melon add 1 -2 tsp licorice powder to it mix well drink this solution once daily

12. EXERCISE : - Improves fitness, energy and mood reduces seizures and impact of epilepsy on one’s life Exercise releases positive feeling hormones into brain increases oxygen flow to brain Go for warm up/ stretching exercises Walk for 45 mins. , 4 times a week Drink water before and after exercise to prevent dehydration Stop and rest if you are feeling tired 13. YOGA: - Alleviates stress - Induces relaxation - Combination of DEEP BREATHING, PHYSICAL POSTURES AND MEDITATION Controls seizures and reduces other epilepsy symptoms - Best yoga poses for epilepsy are: a. Balasana(child’s pose) b. Nadi shodhana(alternate nostril breathing) c. Kapotasana (pigeon pose) d. Sirsasana (headstand)

14. VITAMINS: - Certain vitamins control neurons that cause seizures and anxiety disorders - Consume the following Vitamin supplements after doctor consultation: a. Vitamin E b. Vitamin B 6 c. Vitamin B 1 d. Vitamin D e. Vitamin B 12 15. ACCUPUNCTURE: - “Phenomenon of applying pressure to specific points on the body, by using fine needles” - Acupuncture restores flow of energy throughout the body alters brain activity reduces seizures 16. COUNSELLING TIPS IN PREGNANCY: - Start FOLIC ACID 5 mg daily for 2 months before conception , to reduce risk of AED induced fetal abnormalities - Since some AEDs are associated with hemorrhage risk, give oral Vitamin K 20 mg daily to mother during last month of pregnancy, and Vitamin K (1 mg i. m ) to infant at birth 17. GET ENOUGH SLEEP, AS SLEEP DEPRIVATION TRIGGERS SEIZURES 18. MANAGE STRESS AND AVOID STRESSFUL SITUATIONS

19. IF YOU HAVE SEIZURES REGULARLY, WEAR A ‘MEDICAL ALERT BRACELET’ THIS WILLHELP PEOPLE TO KNOW ABOUT YOUR CONDITION 20. DRINK HALF GLASS OF GRAPE JUICE DAILY 21. LIMIT ALCOHOL INTAKE 22. AVOID SMOKING 23. LOW CALCIUM AND MAGNESIUM TRIGGERS SEIZURES CONSUME FOODS RICH IN THEM 24. AVOID ALL ‘WHITE PRODUCTS’ LIKE: a. White sugar b. White flour c. Table salt d. White rice

25. DO NOT SKIP MEALS, ESPECIALLY BREAKFAST 26. DO NOT CONSUME ARTIFICIAL SWEETENERS/ ADDITIVES 27. TAKE MEDICINES PRESCRIBED BY DOCTOR IN CORRECT DOSAGES IN A TIMELY MANNER 28. DO NOT SKIP TAKING YOUR MEDICINES WITHOUT DOCTOR’S APPROVAL 29. AVOID USAGE OF GINGKO BILOBA AND ST. JOHN’S WORT FOR EPILEPSY , UNLESS UNDER DOCTOR’S ADVICE (SINCE THEY CAN INTERACT WITH AEDs) 30. FOLLOW A KETOGENIC DIET, COMPRISING: a. High fat(nuts, cream, butter) b. Low carbohydrate (starchy fruits, bread, pasta, grains, sugar) c. Adequate protein (pulses, soybean etc. ) d. Helps treat DIFFICULT TO CONTROL (REFRACTORY)

BIBLIOGRAPHY/ REFERENCE : 1. DAVENPORT. J. R; LEACH. P. J; ‘NEUROLOGICAL DISEASE: EPILEPSY’; DAVIDSON’S PRINCIPLES AND PRACTICE OF MEDICINE; 22 ND EDITION; Pg: 1178 -85 2. Tripathi. K. D; “Essentials of medical pharmacology”; 7 th edition; Jaypee Publishers; “Antiepileptic drugs’; Pg: 411 -424 3. Dhillon. S; Sander. W. J; “Clinical pharmacy and therapeutics”; by Roger Walker; 5 th edition; “Epilepsy”; Pg: 489 4. Wells. G. Barbera; ”Epilepsy”; Pharmacotherapy Handbook; by Joseph. T. Dipiro; Pg: 577 5. www. healthline. com 6. www. drugbank. com 7. www. webmd. com 8. http: //www. thelancet. com/journals/abstract/’Top 10 home remedies To deal with Epilepsy’ 9. Razzhaghi. A; “Seizure disorders”; “Comprehensive Pharmacy Review for NAPLEX by LEON SHARGEL”; 8 TH EDITION; Pg: 743 10. Mc. Namara. C. J; “Pharmacotherapy of the Epilepsies”; Goodman & Gilman’s Pharmacological basis of Therapeutics; 11 th edition; Pg: 501

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